Selective ERBB2 inhibitor CGT4255 for adults with ERBB2-altered advanced solid tumors

A Study of a Selective ERBB2 Inhibitor, CGT4255, in Patients With Advanced Solid Tumors With ERBB2 Genetic Alterations or HER2 Overexpression

Phase 1 Interventional Cogent Biosciences, Inc. · NCT07361562

This trial tests a targeted drug called CGT4255 in adults with advanced solid tumors that have ERBB2 (HER2) changes to see if it is safe and shows anti-tumor activity.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment100 (estimated)
Ages18 Years and up
SexAll
SponsorCogent Biosciences, Inc. Industry-sponsored
Drugs / interventionschemotherapy, radiation
Locations6 sites (Grand Rapids, Michigan and 5 other locations)
Trial IDNCT07361562 on ClinicalTrials.gov

What this trial studies

This open-label phase 1/1b trial enrolls adults with locally advanced or metastatic solid tumors harboring ERBB2 alterations, ERBB2 mutations, HER2 overexpression, or NRG1 fusions and includes breast cancer and non–small cell lung cancer cohorts. It uses a dose-escalation then expansion design to define safety, tolerability, and pharmacokinetics, with pharmacodynamic measures and preliminary antitumor activity (RECIST v1.1) as secondary endpoints. Different protocol parts target specific alteration types and tumor groups, and eligibility requires measurable disease plus defined ECOG performance status and laboratory parameters. The study will identify a recommended phase 2 dose and characterize activity in selected molecularly defined subgroups.

Who should consider this trial

Good fit: Adults with measurable, locally advanced or metastatic solid tumors that have documented ERBB2-activating alterations, ERBB2 mutations, HER2 overexpression, or NRG1 fusions who meet the trial's ECOG (0–1 for Part A; 0–2 for Parts B/C) and laboratory criteria are the intended participants.

Not a fit: Patients without ERBB2/HER2 alterations, those who cannot meet ECOG or laboratory requirements, or those who received recent excluded anticancer therapies are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, CGT4255 could shrink tumors or slow disease progression in patients whose cancers are driven by ERBB2 alterations, providing a new targeted treatment option.

How similar studies have performed: Other HER2-targeted therapies have shown clear benefit in HER2-positive breast cancer and some ERBB2-mutant lung cancers, but selective small-molecule ERBB2 inhibitors are still being actively tested with mixed early results.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

1. Have histologically confirmed diagnosis of:

   1. Part A: Locally advanced, metastatic, and/or unresectable solid tumor with documented ERBB2-activating alteration or NRG1 gene fusion in blood and/or tumor or HER2 overexpression in tumor
   2. Part B: Locally advanced, metastatic, and/or unresectable NSCLC with documented ERBB2 mutation in blood and/or tumor
   3. Part C: Locally advanced, metastatic and/or unresectable breast cancer with documented ERBB2 mutation in blood and/or tumor or HER overexpression in tumor
2. Have measurable disease per RECIST v1.1.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1 for Part A. For Parts B and C, ECOG Performance Status must be 0 to 2.
4. Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits.

Exclusion Criteria:

1. Received small molecule chemotherapy or anticancer therapies or radiotherapy within certain timeframes before first dose of study drug.
2. Major surgeries (eg, craniotomy and thoracotomy) within 4 weeks of the first dose of study drug.
3. Treatment with palliative focal radiotherapy (cranial or extracranial) (eg, stereotactic radiosurgery or intensity-modulated radiation therapy) ≤2 weeks before the first dose of study drug; treatment with whole-brain radiotherapy ≤4 weeks before the first dose of study drug.
4. Clinically significant cardiac disease.
5. Resolution of toxicities from prior therapy to ≤Grade 1 (or baseline), including resolution of clinically significant laboratory abnormalities, before the first dose of study drug.
6. Restrictions on use of corticosteroid use to manage neurologic symptoms in different parts of the study.

Where this trial is running

Grand Rapids, Michigan and 5 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Advanced Solid Tumor, AdultERBB2 Altered Breast CancerERBB2 Gene AmplificationHER2 OverexpressionNon-Small Cell Lung CancerHER2ERBB2 genetic alterationsInvestigational Drug
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.